Scientific Abstract

Proposal No. IBD-0074R
Principal Investigator: Marcel A. Behr, M.D.
Applicant Organization: McGill University Health Centre Research Institute (Montreal, Canada)
Project Title: Molecular and immunologic detection of Mycobacterium avium paratuberculosis in Crohn’s disease
Period of Award: December 1, 2003 - March 31, 2006

The hypothesis is that Mycobacterium avium paratuberculosis (MAP) causes a disease in humans that is indistinguishable from Crohn’s.  The applicant does not hypothesize that all Crohn’s is due to MAP, but simply that MAP disease will present as Crohn’s and that patients with MAP disease represent an important subset of persons currently diagnosed and managed as Crohn’s.  In the absence of accurate diagnostic modalities, it is not possible to distinguish these two entities.  As such, the applicant is seeking to solidify the utility of improved diagnostic modalities that may aid in the search for MAP in patients with CD.

Two modalities are to be used in parallel and their results compared and contrasted.  The first modality is an improved form of tissue polymerase chain reaction (PCR), already validated on tissue from sheep with paucibacillary (low numbers of bacteria) paratuberculosis.  The major technical improvement on what has been previously reported is that the tissue DNA extraction step has been greatly modified to improve the ability to capture low numbers of Mycobacterial DNA.  The second modality is immunological study of patients, searching for an interferon-γ response to stimulation of their lymphocytes with MAP proteins.  Here the advance is that most studies of MAP in CD patients have looked for a humoral response, and in the lone study looking at a cellular immunologic response, the sensitin used was from the relatively avirulent Mycobacterium avium avium, rather than the pathogenic MAP.

The expectation is that the implementation of more sensitive diagnostic modalities will translate into a greater proportion of positive results than has been previously reported, thereby facilitating the identification of persons with evidence of MAP infection.  The goal of these studies is not to finally resolve the debate about MAP, but rather to develop sufficient data to recognize the potential utility and limitations of these diagnostic modalities in patients with CD.  The prevalence of positive results with these modalities will be compared among patients with CD and controls with either ulcerative colitis or non-inflammatory bowel disease controls, to determine whether a trend exists suggesting a higher proportion of MAP infection in CD patients than controls.   As well, the concordance between results of the two diagnostic modalities will be assessed.  Results will be compared with classical disease classification systems to suggest whether certain sub-types of CD are more likely to provide positive results, so that future, larger studies may target these patient populations.